Monoamide Derivatives of EDTA Incorporating Pendent Carboxylates or Pyridyls: Synthesis, Metal Binding, and Crystal Structure of a Dinuclear Ca2+ Complex Featuring Bridging Na+ Ions

Abstract

AbstractEDTA is a powerful, cheap and widely‐used chelating unit for a large range of metal ions. To link it covalently to other molecules, the formation of an amide bond using one of the carboxylates is an attractive and simple approach, even though it may compromise metal ion binding as one of the four carboxylate donors is lost. Here we undertake a quantitative study of the metal ion binding of two new mono‐amide derivatives of EDTA, namely AmGly1 and AmPy1, featuring an additional coordinating carboxylate or pyridyl group in the amide, respectively. The compounds are conveniently synthesised through alkylation of the tris‐t‐butyl ester of ethylenediamine‐triacetic acid with the appropriate α‐chloroamide. The switch from carboxylate to amide is found to impact Fe3+ binding the most amongst the metal ions examined (Mg2+, Ca2+, Mn2+, Fe3+, Zn2+), with a drop in log K(ML) of around 10 units in aqueous solution. The affinities for the other metals are less severely affected. Nevertheless, at the physiologically relevant pH of 7.4, their ability to bind Fe3+ is only reduced by around 6 log units when pFe3+ is considered (where [L]:[Fe3+] = 10:1). AmGly1 forms a dinuclear Ca2+ complex which has been characterised crystallographically. It is a C2‐symmetric 2:2 complex featuring a dicapped octahedral coordination geometry around Ca2+. In the crystal, the Ca2(AmGly1)2 units are linked via hydrated Na+ ions coordinated by a number of the oxygen atoms, including the pendent carboxylate.